Polyhydroxy fullerene sunscreen active agents and compositions

ABSTRACT

Sunscreen compositions comprising a dermatologically acceptable carrier and a polyhydroxy fullerene compound are described. The sunscreen compositions can be used to protect a substrate such as the skin of a subject from the effects of ultraviolet radiation.

CONTINUING APPLICATION DATA

This application is a National Phase filing of PCT/US2017/016669, filedFeb. 6, 2017, which claims the benefit of U.S. Provisional PatentApplication Ser. No. 62/290,997, filed Feb. 4, 2016, the disclosures ofeach are hereby incorporated by reference herein.

GOVERNMENT FUNDING

This invention was made with government support under Army Grant#W81XWH-15-1-0580 awarded by the U.S. Department of Defense. Thegovernment has certain rights in the invention.

BACKGROUND

Every year, over one million new cases of skin cancer are diagnosed inthe U.S., outnumbering the total number of all other cancer diagnosescombined, imposing an annual economic burden of $8.1 billion for skincancer treatment. Exposure to UV radiation is the most common, and alsothe most preventable, cause of skin cancers. Skin damage with UVexposure occurs through at least two mechanisms: (i) direct damage toDNA, mainly from UVB (280-320 nm), and (ii) production of free radicalsfrom UVA (320-400 nm), which destroy intracellular components includingDNA, membranes, and proteins.

Sunscreens are the first step in skin cancer prevention. Sunscreenagents include both organic sunscreens and inorganic sunscreens.Inorganic sunscreens include inorganic particles which provideprotection to the skin by directly blocking solar radiation. Examples ofinorganic sunscreens include zinc oxide and titanium dioxide. However, aproblem with inorganic sunscreens is that they give the skin anunnatural whiteness when applied at effective concentrations.

Organic sunscreen compounds are organic compounds which act by absorbingsolar radiation at a particular range of wavelengths, and then emittingthem at a different, less harmful wavelength. Organic sunscreens arecategorized into UV-A sunscreens and UV-B sunscreens, depending on theirabsorption wavelength. The most common UV-A sunscreens are those of thedibenzoylmethane class. UV-B organic sunscreens include those based onbenzophenone, cinnamic acid, salicylic acid, and diphenyl acrylic acid.However, in order to have sunscreen protection over the full range ofharmful wavelengths, sunscreen compositions must include both UV-Asunscreen and UV-B sunscreen compounds, which can increase the cost andaggravate stability problems.

Current organic sunscreen formulations have multiple active ingredients(AIs) and suffer from ephemeral efficacy (requiring frequentreapplication), poor stability, and a tendency toward irritation andphoto-allergies. Common organic UV-absorbers, such as avobenzone andoctisalate, are easily degraded by UV and need stabilizers to functionproperly. Bens G, Sunscreens, in Sunlight, Vitamin D and Skin Cancer, J.Reichrath, Editor. 2014, Landes Bioscience and Springer Science+BusinessMedia, LLC: New York. p. 429-463. Similarly, antioxidants, such ashomosalate, are degraded by radicals or excited electrons generated fromthe UV absorbers. Several common AIs including oxybenzone and homosalateare reported to be endocrine disruptors and to cause skin allergy.Krause et al., Int J Androl, 35(3): p. 424-36 2012. Recent long-termstudies have shown that sunscreen AIs such as oxybenzone reducefertility in humans. Certain AIs, such as retinyl palmitate used forreducing UV-induced skin aging, may even increase skin cancer risk.National Toxicology Program, Natl Toxicol Program Tech Rep Ser.(568):1-352 (2012). These limitations appear to contribute to thefailure of current sunscreens in reducing the incidence of skin cancer.In addition, a recent study suggests that current sunscreens, withoptimal application, provide only partial protection against UV-inducedmelanoma. Viros et al., Nature, 511(7510): p. 478-82 (2014). Further,the traditional antioxidants used in the sunscreens have major drawbacksof a) monofunctionality, i.e., each type of antioxidant is activeagainst only a specific type of free radical such as gallocatechin forsuperoxide; b) low capacity, i.e., neutralizes only one free radical permolecule of antioxidant; c) low stability, i.e., antioxidants such asEGCG undergo auto-oxidation, forming dimers with concomitant generationof free radicals; and d) failure to activate Nrf2; the latter, alsocalled nuclear factor erythroid 2-related factor, is an essentialtranscription factor that regulates expression of phase II antioxidantsand detoxifying enzymes, thereby decreasing inflammation and preventingskin carcinogenesis. Accordingly, there remains a need for moreeffective sunscreen compositions, and particularly sunscreen agents thatcan provide effective sunscreen protection without requiring the use ofmultiple active agents, with good stability, and at relatively lowconcentration.

SUMMARY OF THE INVENTION

The present invention utilizes a novel, safe, multifunctional activeingredient called polyhydroxy fullerenes (PHF) for next-generationsunscreens. PHF absorbs both UVB and UVA, and is a powerful antioxidant.The innovative use of PHF as the AI in sunscreen overcomes the concernsassociated with traditional AIs in current sunscreen formulations.

Polyhydroxy fullerenes (PHF) are water-soluble form of fullerenes.Fullerenes are spherical cages made of carbon atoms with a generalformula of C_(2n), where n can range from 10 to 270. The molecularformula for an unmodified PHF is C_(2n)(OH)_(x); where x is in the rangeof 12 to 40.

PHF is a water-soluble, biocompatible and biodegradable molecule withexcellent antioxidant properties. Krishna et al., Small, 6(20): p.2236-2241 (2010). PHF is a broad spectrum UV absorber (i.e., it absorbsboth UVB and UVA) with its critical wavelength of 381 nm and UVA/UVBratio of 1.6 exceeding the FDA minimum limit of 370 nm and 0.91,respectively. The inventors have shown that PHF absorbs UV withoutgenerating free radicals (Krishna et al., Applied CatalysisB-Environmental, 79(4): p. 376-381 (2008), and can catalyticallyneutralize different types of free radicals (superoxide, nitric oxide,etc.), without any change to its molecular structure. Yin et al.,Biomaterials, 30(4): p. 611-21 (2009). PHF activates the Nrf2 pathway tofortify the body's natural antioxidant system and alleviate allergies.Ye et al., Int J Nanomedicine, 9: p. 2073-87 (2014). The inventorsengineered the PHF molecular structure to further enhance itsantioxidant activity. See U.S. Pat. No. 9,084,989. Most importantly, PHFrepresents an effective, multifunctional sunscreen agent that couldreplace the multiple AIs in current sunscreens. This combinedUV-absorber and antioxidant is simpler, safer, and more stable thancurrent sunscreen formulations.

The inventors have discovered that PHF is a multifunctional activeingredient for sunscreen with superior UV protection properties. The invitro and in vivo studies support use of PHF as a sunscreen activeingredient. Further, they have demonstrated that PHF can be easilyincorporated in a model sunscreen formulation.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 provides a schematic representation of the chemical structure ofa polyhydroxy fullerene (PHF) molecule (x=12 to 42).

FIG. 2 provides a graph showing the UV-Visible absorbance spectra for acommercial SPF60 sunscreen formulation and PHF solution.

FIG. 3 provides images showing how polyhydroxy fullerene (PHF) moleculescan neutralize different types and multiple numbers of free radicalscompared to natural antioxidants such as green tea catechin, which canscavenge only one free radical.

FIGS. 4A-4F provide images showing the ability of PHF to absorb UV andprevent damage to the skin, in a murine model. Histological analysiswith standard H&E staining (a-b), or immunofluorescent staining withanti-Ki-67 to assess proliferation (c, d) or anti-CPD (e, f) to assessDNA damage and rate of photoproduct removal. White circles in a, b;apoptotic sunburn cells.

FIG. 5 provides a graph showing a comparison of blinded scoring for 48hour erythema and edema of skin sections with different topicalapplications. *indicates significance at α=0.01 as compared to control.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a sunscreen composition, comprising adermatologically acceptable carrier and a fullerene compound accordingto the formula C_(2n)(OH)_(t)(NH₂)_(v)(COOH)_(w)(COOM)_(x)O_(y)M_(z),wherein M is an alkali metal, alkaline earth metal, transition metal,post-transition metals or lanthanides, n is a number ranging from 10 to270, t is number ranging from 0 to 60, v is a number ranging from 0 to60, w is a number ranging from 0 to 60, x is a numbering ranging from 0to 60, y is a number ranging from 0 to 30, and z is a number rangingfrom 0 to 30. The present invention also provides methods of using thesunscreen composition to protect a substrate such as the skin of asubject from the effects of ultraviolet radiation.

Definitions

The terminology as set forth herein is for description of theembodiments only and should not be construed as limiting of theinvention as a whole. Unless otherwise specified, “a,” “an,” “the,” and“at least one” are used interchangeably. Furthermore, as used in thedescription of the invention and the appended claims, the singular forms“a”, “an”, and “the” are inclusive of their plural forms, unlesscontraindicated by the context surrounding such.

The terms “comprising” and variations thereof do not have a limitingmeaning where these terms appear in the description and claims.

The recitations of numerical ranges by endpoints include all numberssubsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3,3.80, 4, 5, etc.).

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention pertains. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice for testing of the present invention, the preferredmaterials and methods are described herein. In describing and claimingthe present invention, the following terminology will be used.

As used herein, the term “organic group” is used for the purpose of thisinvention to mean a hydrocarbon group that is classified as an aliphaticgroup, cyclic group, or combination of aliphatic and cyclic groups(e.g., alkaryl and aralkyl groups). In the context of the presentinvention, the term “aliphatic group” means a saturated or unsaturatedlinear or branched hydrocarbon group. This term is used to encompassalkyl, alkenyl, and alkynyl groups, for example.

As used herein, the terms “alkyl”, “alkenyl”, and the prefix “alk-” areinclusive of straight chain groups and branched chain groups and cyclicgroups, e.g., cycloalkyl and cycloalkenyl. Unless otherwise specified,these groups contain from 1 to 20 carbon atoms, with alkenyl groupscontaining from 2 to 20 carbon atoms. In some embodiments, these groupshave a total of at most 10 carbon atoms, at most 8 carbon atoms, at most6 carbon atoms, or at most 4 carbon atoms. Lower alkyl groups are thoseincluding at most 6 carbon atoms. Examples of alkyl groups includehaloalkyl groups and hydroxyalkyl groups.

Unless otherwise specified, “alkylene” and “alkenylene” are the divalentforms of the “alkyl” and “alkenyl” groups defined above. The terms,“alkylenyl” and “alkenylenyl” are used when “alkylene” and “alkenylene”,respectively, are substituted. For example, an arylalkylenyl groupcomprises an alkylene moiety to which an aryl group is attached.

The term “aryl” as used herein includes carbocyclic aromatic rings orring systems. Examples of aryl groups include phenyl, naphthyl,biphenyl, anthracenyl, phenanthracenyl, fluorenyl and indenyl. Arylgroups may be substituted or unsubstituted.

When a group is present more than once in any formula or schemedescribed herein, each group (or substituent) is independently selected,whether explicitly stated or not. For example, for the formula —C(O)—NR₂each R group is independently selected.

As a means of simplifying the discussion and the recitation of certainterminology used throughout this application, the terms “group” and“moiety” are used to differentiate between chemical species that allowfor substitution or that may be substituted and those that do not soallow for substitution or may not be so substituted. Thus, when the term“group” is used to describe a chemical substituent, the describedchemical material includes the unsubstituted group and that group withnonperoxidic O, N, S, Si, or F atoms, for example, in the chain as wellas carbonyl groups or other conventional substituents. Where the term“moiety” is used to describe a chemical compound or substituent, only anunsubstituted chemical material is intended to be included. For example,the phrase “alkyl group” is intended to include not only pure open chainsaturated hydrocarbon alkyl substituents, such as methyl, ethyl, propyl,tert-butyl, and the like, but also alkyl substituents bearing furthersubstituents known in the art, such as hydroxy, alkoxy, alkylsulfonyl,halogen atoms, cyano, nitro, amino, carboxyl, etc. Thus, “alkyl group”includes ether groups, haloalkyls, nitroalkyls, carboxyalkyls,hydroxyalkyls, sulfoalkyls, etc. On the other hand, the phrase “alkylmoiety” is limited to the inclusion of only pure open chain saturatedhydrocarbon alkyl substituents, such as methyl, ethyl, propyl,tert-butyl, and the like.

A “sunscreen composition” as used herein, is meant to include acomposition for topical application to sun-exposed areas of the skinand/or hair of mammals, especially humans. Such a composition may begenerally classified as leave-on or rinse off, and includes any productapplied to a human body including an active agent that protects the skinagainst UV-induced damage, and includes products that also improvingappearance, cleansing, odor control or provide improved generalaesthetics.

The term “dermatologically acceptable”, as used herein, means that thecompositions or components described are suitable for use in contactwith human skin without risk of toxicity, incompatibility, instability,allergic response, and the like.

A “subject,” as used herein, can be any animal, and may also be referredto as the patient. Preferably the subject is a vertebrate animal, andmore preferably the subject is a mammal, such as a domesticated farmanimal (e.g., cow, horse, pig) or pet (e.g., dog, cat). In someembodiments, the subject is a human. A subject in need of protection isa subject who is likely to be exposed to strong sunlight withpotentially damaging UV radiation in the near future.

The language “effective amount” or “protective amount” refers to anontoxic but sufficient amount of the composition used in the practiceof the invention that is effective to decrease or prevent skin injuryfrom exposure to sunlight and/or ultraviolet radiation. That result canbe reduction and/or alleviation of the signs, symptoms, or other resultsfrom exposure to sunlight and/or ultraviolet radiation. An appropriatetherapeutic amount in any individual case may be determined by one ofordinary skill in the art using routine experimentation.

Polyhydroxy Fullerenes

Polyhydroxy fullerenes (PHF) are water-soluble form of fullerenes. Thestructure of unmodified polyhudroxyfullerenes is shown in FIG. 1.Fullerenes are spherical cages made of carbon atoms with a generalformula of C_(2n), where n can range from 10 to 270. The molecularformula for a relatively unmodified PHF is C_(2n)(OH)_(t)O_(y)M_(z);where M is an alkali metal, alkaline earth metal, or transition metal; tis in the range of 8 to 60; y is in the range of 0 to 30; and z is inthe range of 0 to 30.

The present invention is directed to PHF compositions that have theability to absorb ultraviolet radiation, and exhibit an electronscavenging ability. The functionality of PHF influences its electronscavenging ability. PHFs commonly contain functional groups such ashydroxyl, hemiketal, epoxide and carbonyl groups that modify theelectronic properties of the PHFs. It was discovered that PHFs whichhave a low ratio (<0.3) of non-hydroxyl functional groups to hydroxylfunctional groups have enhanced electron scavenging ability, whereasPHFs that display a ratio higher than 0.3 have decreased electronscavenging ability.

PHFs can be of a single size or can be mixtures of different fullerenesizes. The fullerene cage can be C₂₈, C₃₂, C₄₄, C₅₀, C₅₈, C₆₀, C₇₀, C₈₄,C₂₅₀, C₅₄₀, or any other fullerene. These correspond to polyhydroxyfullerenes of the claimed invention wherein n is 14, 16, 22, 25, 29, 30,35, 42, 125, and 270, respectively. The PHFs have an average of about1.25 to 3 C atoms per OH group, which is equivalent to about 27 to about48 OH groups on a C₆₀ cage. The PHFs are often C₆₀ molecules due totheir commercial availability, but other fullerene cages such as C₇₀,C₈₂ or their mixtures or other PHFs can be used in various embodimentsof the invention. The PHFs have C—C single bonds that can be observed byFourier transform infrared spectroscopy (FTIR). Other functional groupsare primarily carbons of a hemiketal and carbonyl structure. PHFs canalso contain epoxy groups and ester groups.

In one aspect, the present invention provides a sunscreen composition,comprising a dermatologically acceptable carrier and a fullerenecompound according to the formulaC_(2n)(OH)_(t)(NH₂)_(v)(COOH)_(w)(COOM)_(x)O_(y)M_(z), wherein M is analkali metal, alkaline earth metal, transition metal, post-transitionmetal or lanthanide, n is a number ranging from 10 to 270, t is numberranging from 0 to 60, v is a number ranging from 0 to 60, w and x are anumber ranging from 0 to 60, y is a number ranging from 0 to 30, and zis a number ranging from 0 to 30. The number of fullerene carbons (C)hydroxyl (OH), amine (NH₂), carboxyl (COOH), metal carboxylate (COOM),oxygen (O) and metal (M) groups can all vary based on the rangesprovided.

In some embodiments, the polyhydroxy fullerene is a compound accordingto the formula C_(2n)(OH)_(t)O_(y)M_(z), which corresponds to thebroader formula wherein v, w, and x are 0. In other embodiments, thepolyhydroxy fullerene is a compound according to formula C_(2n)(OH)_(t),which corresponds to the broader formula wherein t is 1 to 60, and v, w,x, y, and z are 0. In further embodiments, the polyhydroxy fullerene isa compound according to the formula C_(2n)(OH)_(t)(NH₂)_(v)O_(y)M_(z),which corresponds to the broader formula wherein w and x are 0. In yetfurther embodiments, the polyhydroxy fullerene is a compound accordingto the formula C_(2n)(OH)_(t)(COOH)_(w)O_(y)M_(z), which corresponds tothe broader formula wherein v and x are 0. In additional embodiments,the polyhydroxy fullerene is a compound according to the formulaC_(2n)(OH)_(t)(COOM)_(x)O_(y)M_(z), which corresponds to the broaderformula wherein v and w are 0.

The number of hydroxyl (OH), amine (NH₂), carboxyl (COOH), metalcarboxylate (COOM), oxygen (O) and metal (M) groups can all vary. Forexample, for hydroxyl groups, amine groups, carboxyl groups, and metalcarboxylate groups, the number can range from 0 to 60, 1 to 60, 8 to 60,12 to 60, 20 to 60, 0 to 50, 1 to 50, 8 to 50, 12 to 50, 20 to 50, 0 to40, 1 to 40, 8 to 40, 12 to 40, 20 to 40, 0 to 30, 1 to 30, 8 to 30, 12to 30, or 20 to 30, or any other ranges within 0 to 60. For the oxygenand metal groups, the number can range from 0 to 30, 1 to 30, 4 to 30, 8to 30, 12 to 30, 0 to 20, 1 to 20, 4 to 20, 8 to 20, 12 to 20, 0 to 10,1 to 10, and 4 to 10.

Other potential structures for functionalized polyhydroxy fullerenes arealso within the scope of the present invention. In some embodiments, thepolyhydroxyfullerenes have a formula of C_(2n)(OH)_(t)O_(y)M1_(a)M2_(b);where M1 and M2 are different alkali metals, alkaline earth metals,transition metals, post-transition metal or lanthanide; t is in therange of 0 to 60; y, a and b are in the range of 0 to 30.

In some embodiments, the polyhydroxy fullerenes include carbon orpolymer strands bound to the surface of the fullerene cage. The carbonor polymer strands can include polyethylene, polyethylene glycol,polyanhydrides, polyesters, and polyolefins. For example in someembodiments, C_(2n)[C_(m)O_(p)H_(q)](OH)_(t)O_(y)M_(z); where(OH)_(t)O_(y)M_(z) are attached to fullerene cage via the one or morecarbon or polymer chains [C_(m)O_(p)H_(q)]; m is in the range of 1 to 30and p is in the range of 0 to 15, q is in the range of 2 to 60; n is inthe range of 10 to 270, M is an alkali metal, alkaline earth metal,transition metal, post-transition metal or lanthanide; t is in the rangeof 0 to 60; y, z are in the range of 0 to 30. In other embodiments, thepolyhydroxy fullerene is a compound according toC_(2n)[C_(m)O_(p)H_(q)](COOH)_(r)(COOM)_(s)(OH)_(t)O_(y)M_(z); wherecarboxylic acid or metal salts are attached directly to fullerene cageor via the one or more carbon or polymer chains [C_(m)O_(p)H_(q)]; m isin the range of 1 to 30 and p is in the range of 0 to 15, q is in therange of 2 to 60; n is in the range of 10 to 270, r, s and t are in therange of 0 to 60; M is an alkali metal, alkaline earth metal, transitionmetal, post-transition metal or lanthanide; x is in the range of 0 to60; y, z are in the range of 0 to 30. In further embodiments, thepolyhydroxy fullerene is a compound according toC_(2n)[C_(m)O_(p)H_(q)](OH)_(t)(NH₂)_(v)O_(y)M_(z); where amine groupsare attached directly to fullerene cage or via the one or more carbon orpolymer chains [C_(m)O_(p)H_(q)]; m is in the range of 1 to 30 and p isin the range of 0 to 15, q is in the range of 2 to 60; n is in the rangeof 10 to 270, t is in the range of 0 to 60, v is in the range of 1 to60, M is an alkali metal, alkaline earth metal, transition metal,post-transition metal or lanthanide; and y and z are in the range of 0to 30.

In some embodiments, the invention provides a sunscreen compositioncomprising a dermatologically acceptable carrier and a polymer-bearingfullerene compound according to the formula C_(2n)[C_(m)O_(p)H_(q)](OH)_(v)(COOH)_(w)(COOM)_(x)O_(y)M_(z), wherein M is an alkali metal,alkaline earth metal, transition metal, post-transition metal orlanthanide; n is a number ranging from 10 to 270, the one or morepolymer chains [C_(m)O_(p)H_(q)] in which m is in the range of 1 to 30and p is in the range of 0 to 15, q is in the range of 2 to 60, v isnumber ranging from 0 to 60, w is a number ranging from 0 to 60, x is anumbering ranging from 0 to 60, y is a number ranging from 0 to 30, andz is a number ranging from 0 to 30.

Any of the above functionalized fullerenes can be prepared as endohedralmetallofullerenes. See for example Lu et al., Chem Commun (Camb).,50(94), pp. 14701-15 (2014), and Lu et al., Chem Soc Rev., 41(23), pp.7723-60 (2012), the disclosures of which is incorporated herein byreference. Endohedral metallofullerenes have been made using a varietyof different metals and rare earth metals, such as gadolinium, scandium,scandium-titanium, samarium, yttrium, neodymium, dysprosium, erbium, andlutetium. For example, Gd@C₆₀, Gd₃N@C60, and Sc₃N@C₈₀ are typicalendohedral fullerenes.

Polyhydroxy fullerenes (PHF) may be synthesized by synthetic routes thatinclude processes similar to those well known in the chemical arts,particularly in light of the description contained herein. See forExample U.S. Pat. No. 9,084,989, and U.S. Patent Publication No.2007/0202413, the disclosures of which are incorporated herein byreference. A number of fullerenes are also commercially available. Seefor example the Fullerene Supplier Database provided online byNanowerk™.

The sun protection factor (SPF rating) is a measure of the fraction ofsunburn-producing UV rays that reach the skin. For example, “SPF 15”means that 1/15th of the burning radiation will reach the skin, assumingsunscreen is applied evenly at a thick dosage of 2 milligrams per squarecentimeter (mg/cm²). A user can determine the effectiveness of asunscreen “by multiplying the SPF factor by the length of time it takesfor him or her to suffer a burn without sunscreen. The PHF-basedsunscreens described herein are both UVB and UVA absorbers, and cantherefore also labeled with “SPFXX” (for UVB) and “Broad spectrum” (forUVA).

Sunscreen compositions according to the present invention can beformulated to achieve a variety of different SPFs. For example, thesunscreen formulations can have an in vitro or in vivo SPF of at least5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 100, 105, 110, 115, 120, 125, 135, 150, 175, 200, 225, 250, 300.325, 350, or higher (or in a range between any of these values).

Compositions of the present invention may, according to certainembodiments, be essentially free of UV-absorbing sunscreen agents otherthan PHF. By “essentially free of non-PHF UV-absorbing sunscreenagents,” it is meant that, in this embodiment, the compositions do notcontain non-PHF UV-absorbing sunscreen agents in an amount effective toprovide the compositions with an SPF of greater than 2. For example, thecompositions of the invention will contain about 0.5% or less, or about0.1% or less, of such non-PHF UV-absorbing sunscreen agents. The phrase“essentially free,” as used herein, refers to an amount less than orequal to 0.5, 0.1, 0.05 or 0.01 wt. %.

Additional Sunscreen Active Agents

The compositions of the subject present disclosure may optionallycontain another sunscreen active agent in combination with thepolyhydroxy fullerene. As used herein, “sunscreen active” includes bothsunscreen agents and physical sunblocks. Suitable sunscreen actives maybe organic or inorganic.

A wide variety of conventional organic or inorganic sunscreen activesare suitable for use herein. In one embodiment, the compositioncomprises from about 0.1% to about 20%, more typically from about 0.5%to about 10% by weight of the composition, of the sun screen active.Exact amounts will vary depending upon the sunscreen chosen and thedesired Sun Protection Factor (SPF).

As examples of organic sunscreen agents which are active in UV-A and/orUV-B, there may be mentioned in particular those designated below bytheir CTFA name: para-aminobenzoic acid derivatives: PABA, Ethyl PABA,Ethyl Dihydroxypropyl PABA, Ethylhexyl Dimethyl PABA sold in particularunder the name “ESCALOL 507” by ISP, Glyceryl PABA, PEG-25 PABA soldunder the name “UVINUL P25” by BASF, salicyclic derivatives: Homosalatesold under the name “EUSOLEX HMS” by RONAIEM INDUSTRIES, EthylhexylSalicylate sold under the name “NEO HELIOPAN OS” by HAARMANN and REIMER,Dipropyleneglycol Salicylate sold under the name “DIPSAL” by SCHER, TEASalicylate, sold under the name “NEO HELIOPAN TS” by HAARMANN andREIMER, and Octisalate, dibenzoylmethane derivatives: ButylMethoxydibenzoylmethane sold in particular under the trademark “PARSOL1789” by HOFFMANN LA ROCHE, Isopropyl Dibenzolylmethane, cinnamicderivatives: Ethylhexyl Methoxycinnamate sold in particular under thetrademark “PARSOL MCX” by HOFFMANN LA ROCHE, Isopropyl MethoxyCinnamate, Isoamyl Methoxy Cinnamate sold under the trademark “NEOHELIOPAN E 1000” by HAARMANN and REIMER, Cinoxate, DEA Methoxycinnamate,Diisopropyl Methylcinnamate, Glyceryl Ethylhexanoate Dimethoxycinnamate,β,β′-diphenylacrylate derivatives: Octocrylene sold in particular underthe trademark “UVINUL N539” by BASF, Etocrylene, sold in particularunder the trademark “UVINUL N35” by BASF, benzophenone derivatives:Avonbenzone, Benzophenone-1 sold under the trademark “UVINUL 400” byBASF, Benzophenone-2 sold under the trademark “UVINUL D50” by BASF,Benzophenone-3 or Oxybenzone, sold under the trademark “UVINUL M40” byBASF, Benzophenone-4 sold under the trademark “UVINUL MS40” by BASF,Benzophenone-5, Benzophenone-6 sold under the trademark “HELISORB 11” byNORQUAY, Benzophenone-8 sold under the trademark “SPECTRA-SORB UV-24” byAMERICAN CYANAMID, Benzophenone-9 sold under the trademark “UVINULDS-49” by BASF, Benzophenone-12, benzylidene camphor derivatives:Ecamsule, 3-Benzylidene Camphor, 4-Methylbenzylidene Camphor sold underthe name “EUSOLEX 6300” by MERCK, Benzylidene Camphor Sulphonic Acid,Camphor Benzalkonium Methosulphate, Terephthalylidene DicamphorSulphonic Acid, Polyacrylamidomethyl Benzylidene Camphor,phenylbenzimidazole derivatives: Phenylbenzimidazole Sulphonic Acid soldin particular under the trademark “EUSOLEX 232” by MERCK,Benzimidazilate sold under the trademark “NEO HELIOPAN AP” by HAARMANNand REIMER, triazine derivatives: Anisotriazine sold under the trademark“TINOSORB S” by CIBA GEIGY, Ethylhexyl triazones sold in particularunder the trademark “UVINUL T150” by BASF, Diethylhexyl ButamidoTriazone sold under the trademark “UVASORB HEB” by SIGMA 3V,phenylbenzotriazole derivatives: Drometrizole Trisiloxane sold under thename “SILATRIZOLE” by RHODIA CHIMIE, anthranilic derivatives: Menthylanthranilate sold under the trademark “NEO HELIOPAN MA” by HAARMANN andREIMER, imidazoline derivatives: Ethylhexyl DimethoxybenzylideneDioxoimidazoline Propionate, benzalmalonate derivatives:Polyorganosiloxane with benzalmalonate functional groups sold under thetrademark “PARSOL SLX” by HOFFMANN LA ROCHE, and mixtures thereof.others: dihydroxycinnamic acid derivatives (umbelliferone,methylumbelliferone, methylaceto-umbelliferone); trihydroxy-cinnamicacid derivatives (esculetin, methylesculetin, daphnetin, and theglucosides, esculin and daphnin); hydrocarbons (diphenylbutadiene,stilbene); dibenzalacetone and benzalacetophenone; naphtholsulfonates(sodium salts of 2-naphthol-3,6-disulfonic and of2-naphthol-6,8-disulfonic acids); di-hydroxynaphthoic acid and itssalts; o- and p-hydroxybiphenyldisulfonates; coumarin derivatives(7-hydroxy, 7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole,phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles);quinine salts (bisulfate, sulfate, chloride, oleate, and tannate);quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline);uric and violuric acids; tannic acid and its derivatives (e.g.,hexaethylether); (butyl carbotol) (6-propyl piperonyl)ether;hydroquinone.

Organic non-PHF sunscreen agents which are more particularly preferredare chosen from the following compounds: Ethylhexyl Salicylate, ButylMethoxydibenzoylmethane, Ethylhexyl Methoxycinnamate, Octocrylene,Phenylbenzimidazole Sulphonic Acid, Terephthalylidene DicamphorSulphonic, Benzophenone-3, Benzophenone-4,Benzophenone-5,4-Methylbenzylidene camphor, Benzimidazilate,Anisotriazine, Ethylhexyl triazone, Diethylhexyl Butamido Triazone,Methylene bis-Benzotriazolyl Tetramethylbutylphenol, DrometrizoleTrisiloxane, and mixtures thereof. In some embodiments, the organicsunscreen agents include PABA and its derivatives, such as 2-Ethylhexylp-dimethylamino-benzoate, Octinoxate, Camphor derivatives, such as3-(4″Trimethylammonium)-benzyliden-bornan-2-on-methylsulfate,Octocrylene, Octylsalicylate (Octisalate), Benzophenone-3 (Oxybenzone),Benzophenore-4 or 8, Avobenzone, Ecamsule, Silatrizol, and Homosalate.

The inorganic sunscreen agents which may be used in the compositionaccording to the present disclosure are particles of coated or uncoatedmetal oxides such as for example nanopigments of titanium oxide(amorphous or crystallized in the form of rutile and/or anatase), iron,zinc, zirconium or cerium oxides and mixtures thereof. Coating agentsare moreover alumina, silica, and/or aluminum stearate. Suchnanopigments of metal oxides, coated or uncoated, are in particulardescribed in EP-A-O-518,772 and EP-A-O-518,773. One preferred TiO₂/ZnO₂sunscreen agent is OPTISOL, proposed by Oxonica

When used herein, the inorganic sunscreens are present in the amount offrom about 0.01% to about 20%, preferably from about 0.1% to about 10%,more preferably from about 1% to about 5%, by weight of the composition.

Anti-Oxidants/Radical Scavengers

In some embodiments, the sunscreen compositions can include ananti-oxidant/radical scavenger. In one embodiment, the compositioncomprises from about 0.01% to about 10%, more preferably from about 0.1%to about 5%, of an anti-oxidant/radical scavenger.

Anti-oxidants/radical scavengers such as retinyl palmitate, ascorbicacid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbicacid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbylphosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherolsorbate, tocopherol acetate, other esters of tocopherol, butylatedhydroxy benzoic acids and their salts, Vitamin B compounds,N-acetyl-D-glucosamine, glucosyl hesperidin, hexamidine compounds,ascorbyl glucoside, palmitoyl-lysine-threonine-threonine-lysine-serine,butylated hydroxytoluene, cetyl betaine, bisabolol, theophylline,undecenoyl phenylalanine, cetyl pyridinium chloride, dihydroxyacetone,panthenol, butyl methoxydibenzoylmethane, glycyrrhizic acid,glycyrrhetinic acid, butylated hydroxyanisole, tetrahydrocurcumin,ergothioneine, octadecenedioic acid, retinyl propionate, yeast extract,Metalloenzymes, such as superoxide dismutase, perborate, thioglycolates,persulfate salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(commercially available under the tradename Trolox®), gallic acid andits alkyl esters, especially propyl gallate, uric acid and its salts andalkyl esters, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine),nordihydroguaiaretic acid, bioflavonoids, sulfhydryl compounds (e.g.,glutathione), dihydroxy fumaric acid and its salts, lysine pidolate,arginine pilolate, amino acids, silymarin, lysine, 1-methionine,proline, superoxide dismutase, sorbic acids and its salts, lipoic acid,olive extracts, tea extracts, polyphenols such as proanthocyanidine frompine bark, carotenoids, curcumin compounds such as tetrahydrocurcumin,OCTA (L-2-oxo-4-thiazolidine carboxylic acid), glutathione, melanin,green tea extracts, rosemary extracts and grape skin/seed extracts maybe used.

Antioxidants which are more particularly preferred are chosen from thefollowing compounds: Vitamins, such as vitamin E, K and C; Polyphenols,such as green tea polyphenols; Flavonoids; Catechins; Salicyclic acidderivatives, such as Homosalate and Octisalate; and Epigallocatechingallate (EGCG).

Encapsulation

In some embodiments, the polyhydroxy fullerene, alone or in combinationwith other active ingredients and antioxidants, can be encapsulated inpolymeric or inorganic matrices and combination of polymeric andinorganic matrices. The encapsulation can be core-shell structure withPHF in the core or the PHF can be dispersed in the matrix of theencapsulating material. Encapsulation can be used to provide morecontrolled release and/or increased stability. Some examples ofpolymeric matrices are polylactic acid (PLA); polyglycolic acid (PGA);poly (lactic-co-glycolic) acid (PLGA); polyethylene glycol (PEG);polystyrene (PS); polycaprolactone (PCL); poly methyl methacrylate(PMMA); polyvinyl alcohol (PVA); Polyvinylpyrrolidone (PVP); Eudragitpolymers; cellulose and chitosan. Some examples of inorganic matricesare silica, titanium dioxide, zinc oxide, vanadium oxide, tungstenoxide, cerium oxide, and a combination of these.

Additional Ingredients

In some embodiments, additional ingredients can be included in thesunscreen composition beyond the polyhydroxy fullerene and thedermatologically acceptable carrier. For example, the sunscreencomposition can include a safe and effective amount of a conditioningagent selected from, for example, humectants, moisturizers, and skinconditioners. A variety of these materials can be employed and in oneembodiment can be present at a level of from about 0.01% to about 20%,more preferably from about 0.1% to about 10%, and still more preferablyfrom about 0.5% to about 7%, by weight of the composition. Thesematerials can include, but are not limited to, guanidine, urea, glycolicacid, glycolate salts (e.g. ammonium and quaternary alkyl ammonium),salicylic acid, lactic acid, lactate salts (e.g., ammonium andquaternary alkyl ammonium), aloe vera in any of its variety of forms(e.g., aloe vera gel), polyhydroxy alcohols such as sorbitol, mannitol,xylitol, erythritol, glycerol, hexanetriol, butanetriol, propyleneglycol, butylene glycol, hexylene glycol and the like, polyethyleneglycols, sugars (e.g., melibiose), starches, sugar and starchderivatives (e.g., alkoxylated glucose, fructose, glucosamine),hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine,panthenol, allantoin, petroleum and mixtures thereof. Also useful hereinare the propoxylated glycerols described in U.S. Pat. No. 4,976,953.Preferably, the conditioning agent is selected from urea, guanidine,sucrose polyester, panthenol, dexpanthenol, allantoin, glycerol, andcombinations thereof.

Humectants can be selected from the group consisting of polyhydricalcohols, water soluble alkoxylated nonionic polymers, and mixturesthereof. Polyhydric alcohols useful herein include polyhydroxy alcoholsaforementioned and glycerin, hexylene glycol, ethoxylated glucose,1,2-hexane diol, dipropylene glycol, trehalose, diglycerin, maltitol,maltose, glucose, fructose, sodium chondroitin sulfate, sodiumhyaluronate, sodium adenosine phosphate, sodium lactate, pyrrolidonecarbonate, glucosamine, cyclodextrin, and mixtures thereof. Watersoluble alkoxylated nonionic polymers useful herein include polyethyleneglycols and polypropylene glycols having a molecular weight of up toabout 1000 such as those with CTFA names PEG-200, PEG-400, PEG-600,PEG-1000, PPG-12/SMDI copolymer and mixtures thereof.

In certain embodiments, the composition includes a pigment suitable forproviding color or hiding power. The pigment suitable for providingcolor or hiding power may be composed of iron oxides, including red andyellow iron oxides, titanium dioxide, ultramarine and chromium orchromium hydroxide colors, and mixtures thereof. The pigment may be alake pigment, e.g., an organic dye such as azo, indigoid,triphenylmethane, anthraquinone, and xanthine dyes that are designatedas D&C and FD&C blues, browns, greens, oranges, reds, yellows, etc.,precipitated onto inert binders such as insoluble salts. Examples oflake pigments include Red #6, Red #7, Yellow #5 and Blue #1. The pigmentmay be an interference pigment. Examples of interference pigmentsinclude those containing mica substrates, bismuth oxycloride substrates,and silica substrates, for instance mica/bismuth oxychloride/iron oxidepigments commercially available as CHROMALITE pigments (BASF), titaniumdioxide and/or iron oxides coated onto mica such as commerciallyavailable FLAMENCO pigments (BASF), mica/titanium dioxide/iron oxidepigments including commercially available KTZ pigments (Kobo products),CELLINI pearl pigments (BASF), and borosilicate-containing pigments suchas REFLECKS pigments (BASF).

The compositions of the present invention may further comprise one ormore other cosmetically active agent(s). A “cosmetically active agent”is a compound that has a cosmetic or therapeutic effect on the skin,e.g., agents to treat wrinkles, acne, or to lighten the skin. Thecosmetically active agent will typically be present in the compositionof the invention in an amount of from about 0.001% to about 20% byweight of the composition, e.g., about 0.01% to about 10% such as about0.1% to about 5% by weight of the composition.

Protection from Ultraviolet Light Using Polyhydroxy Fullerene SunscreenCompositions

The present invention includes methods of using the PHF sunscreencompositions described herein to protect a substrate (e.g., the skin ofa subject) from damage caused by sunlight or other sources ofultraviolet radiation. The method includes use of any of the PHFsunscreen compositions described herein. Accordingly, in one aspect, thepresent invention provides a method of protecting a substrate from theeffects of ultraviolet light, comprising administering an effectiveamount of a sunscreen composition comprising a dermatologicallyacceptable carrier and a fullerene compound according to the formulaC_(2n)(OH)_(t)(NH₂)_(v)(COOH)_(w)(COOM)_(x)O_(y)M_(z), wherein M is analkali metal or alkaline earth metal, n is a number ranging from 10 to270, t is number ranging from 0 to 60, v is a number ranging from 0 to60, w is a number ranging from 0 to 60, x is a numbering ranging from 0to 60, y is a number ranging from 0 to 30, and z is a number rangingfrom 0 to 30. In some embodiments, the substrate is the skin of asubject in need thereof.

In some embodiments, the substrate is the skin or hair of a subject. Inother embodiments, the substrate is the surface of a plant, such asleaves or flowers, or the surface of a fruit. In other embodiments, thesubstrate is a non-living article. Examples of non-living articlesinclude wood, paints, natural and man-made fibers, plastics, and otherobjects susceptible to damage by ultraviolet radiation.

Administration involves applying the sunscreen composition to thesubstrate. Topical administration is administration to the skin of asubject. The sunscreen composition can be applied manually, or using adevice, and can be applied to a portion of the substrate (e.g., the skinof the subject), all of the substrate, or portions of the substrate thatwill be exposed to sunlight or another source of UV radiation (e.g., awelding arc). The best sunscreen protection is achieved by application15 to 30 minutes before exposure, followed by one reapplication 15 to 30minutes after exposure begins. Further reapplication is necessary onlyafter activities such as swimming, sweating, and rubbing. The statedprotection factor requires that 2 μL of sunscreen be applied per squarecentimeter of exposed skin. In some embodiments, topical administrationis carried out only on a subject who is at risk of injury from sunlightor ultraviolet radiation. A subject can be at risk or in need thereof ifthey are planning on or expected to be exposed to sunlight orultraviolet radiation, or a subject who has a condition that makes themparticularly susceptible to injury from sunlight or ultravioletradiation, such as being an albino or taking medication (e.g., someantibiotics, contraceptives, or tranquilizers) that causes increasedsensitivity to sunlight.

As used herein, the term “protection” refers to a decrease in damage,tissue injury and/or symptoms of tissue injury resulting from exposureof a substrate (e.g., skin) to sunlight or other sources of damagingultraviolet radiation. The decrease in damage or tissue injury and/orsymptoms can vary in degree. For example, in some embodiments, thedecrease is at least a 50% decrease, at least a 60% decrease, at least a70% decrease, at least an 80% decrease, at least a 90% decrease, or a100% decrease, which can also be referred to as prevention of injury.Tissue injury resulting from exposure to sunlight is also known as“sunburn.” Typically, symptoms of sunburn include initial redness(erythema), followed by varying degrees of pain, proportional inseverity to both the duration and intensity of exposure. Other symptomscan include edema, itching, peeling skin, rash, nausea, fever, chills,and syncope. The symptoms of sunburn represent a reaction of the body toDNA damage. Accordingly, protecting a subject from tissue injury fromsunlight or other sources of UV radiation can also decrease thelikelihood that the subject will develop cancer, and in particular skincancer (e.g., melanoma).

Dermatologically Acceptable Carriers for Sunscreen Compositions

The sunscreen compositions of the present invention includes adermatologically acceptable carrier that can be a liquid, lotion,ointment, cream, foam, scrub, gel, soap bar or toner. Non-limitingexamples of such sunscreen compositions include leave-on skin lotions,creams, antiperspirants, deodorants, lipsticks, foundations, mascara,sunless tanners and sunscreen lotions and wash-off shampoos,conditioners, shower gels, toilet bars. In some cases, the sunscreencomposition is clear. Also, the sunscreen composition may be a spray-onsunscreen composition.

The total amount of the polyhydroxy fullerene (and optionally otheractive sunscreen agents) can vary depending on the desired SPF andoverall UV filtering strength of a final sunscreen composition. In oneaspect, the total amount of the active agents in the sunscreencombination is about 50, 40, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12,11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, or 0.1 wt. %.

In certain embodiments the sunscreen composition has a pH that is fromabout 4.0 to about 8.0, such as from about 5.5 to about 7.0.

The inventors have designed a model sunscreen to incorporate PHF thatcontains standard ingredients such as viscosity enhancers (HPMC),oils/emollients (cetyl alcohol), humectants (glycerin), gelling agents,film formers, and emulsifiers (Brij 99 and Brij 52). PHF is easilyincorporated in the model formulation and provides uniform surfacecoverage. Additionally sustained release PHF containing particles forrelease over an 8 hour period may be added.

Oils/Emollients

Examples of oils/emollients that may be included in the sunscreencompositions include: hydrocarbon-based oils of plant origin, such asliquid triglycerides of fatty acids containing from 4 to 10 carbonatoms, for instance heptanoic or octanoic acid triglycerides, oralternatively, for example, sunflower oil, corn oil, soybean oil, marrowoil, grapeseed oil, sesameseed oil, hazelnut oil, apricot oil, macadamiaoil, arara oil, coriander oil, castor oil, avocado oil, caprylic/capricacid triglycerides, for instance those sold by the company StearineriesDubois or those sold under the names Miglyol 810, 812 and 818 by thecompany Dynamit Nobel, jojoba oil, shea butter oil and caprylyl glycol;synthetic esters and ethers, especially of fatty acids, for instancePurcellin oil, 2-octyldodecyl stearate, 2-octyldodecyl erucate,isostearyl isostearate; hydroxylated esters, for instance isostearyllactate, octyl hydroxystearate, octyldodecyl hydroxystearate,diisostearyl malate or triisocetyl citrate; fatty alcohol heptanoates,octanoates or decanoates; polyol esters, for instance propylene glycoldioctanoate, neopentyl glycol diheptanoate and diethylene glycoldiisononanoate; and pentaerythritol esters, for instance pentaerythrityltetraisostearate, or isopropyl lauroyl sarcosinate, sold especiallyunder the trade name Eldew SL 205 by the company Ajinomoto; linear orbranched hydrocarbons, of mineral or synthetic origin, such as volatileor non-volatile liquid paraffins, and derivatives thereof, petroleumjelly, polydecenes, isohexadecane, isododecane, hydrogenatedpolyisobutene such as Parleam oil, or the mixture of n-undecane (C₁₁)and of n-tridecane (C₁₃) sold under the reference Cetiol UT by thecompany Cognis; fluoro oils that are partially hydrocarbon-based and/orsilicone-based, for instance those described in document JP-A-2 295 912;silicone oils, for instance volatile or non-volatile polymethylsiloxanes(PDMS) with a linear or cyclic silicone chain, which are liquid or pastyat room temperature, in particular volatile silicone oils, especiallycyclopolydimethylsiloxanes (cyclomethicones) such ascyclohexadimethylsiloxane and cyclopentadimethylsiloxane;polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, whichare pendent or at the end of a silicone chain, these groups containingfrom 2 to 24 carbon atoms; phenyl silicones, for instance phenyltrimethicones, phenyl dimethicones,phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones,diphenylmethyldiphenyltrisiloxanes or 2-phenylethyl trimethylsiloxysilicates, and polymethylphenylsiloxanes; mixtures thereof.

Additional examples include benzoic acid esters of C₉-C₁₅ alcohols,isononyl iso-nonanoate, C₁₂-C₁₅ alkyl benzoate, or any combinationsthereof.

Specific examples of oils/emollients include cocoglyceride,cyclomethicone, dimethicone, dicapryl maleate, caprylic/caprictriglyceride, isopropyl myristate, octyl stearate, isostearyl linoleate,lanolin oil, coconut oil, cocoa butter, olive oil, avocado oil, aloeextracts, jojoba oil, castor oil, fatty acid, oleic acid, stearic acid,fatty alcohol, cetyl alcohol, hexadecyl alcohol, diisopropyl adipate,hydroxybenzoate esters, benzoic acid esters of C₉-C₁₅ alcohols, isononyliso-nonanoate, alkanes, mineral oil, silicone, dimethyl polysiloxane,ether, polyoxypropylene butyl ether, polyoxypropylene cetyl ether,C₁₂-C₁₅ alkyl benzoate, aryl alkyl benzoate, Isopropyl Lauroylsarcosinate, and any combinations thereof.

Examples of hydrophilic organic solvents that may be included in thesunscreen compositions include: monohydric C₁-C₈ alcohols such asethanol, propanol, butanol, isopropanol, isobutanol; Polyethyleneglycols from 6 to 80 ethylene oxides such as propylene glycol, isopreneglycol, butylene glycol, glycerol, sorbitol; and mono or di-alkylisosorbides such as dimethyl isosorbide.

Examples of amphiphilic organic solvents include: polypropylene glycol(PPG) like propylene glycol alkyl ester or alkyl ether of PPG likePPG-23 oleyl ether and PPG-36 oleate.

The total amount of oils/emollient present in the compositions istypically about 0.1, 0.5, 1.0, or 2.5 wt. % to about 5.0, 7.5, 10.0,15.0, 20.0, or 30 wt. % of the total weight of the composition.

Film Formers

Film-formers are often incorporated into sunscreen compositions toensure even coverage of the UV filters and can be used to render thecomposition water resistant. The film former is typically a hydrophobicmaterial that imparts film forming and/or waterproofing characteristics.One such agent is polyethylene, which is available from New PhaseTechnologies as Performalene® 400, a polyethylene having a molecularweight of 400. Another suitable film former is polyethylene 2000(molecular weight of 2000), which is available from New PhaseTechnologies as Performalene®. Yet, another suitable film former issynthetic wax, also available from New Phase Technologies as Performa®V-825. Other typical film-formers include acrylates/acrylamidecopolymer, acrylates copolymer, acrylates/C₁₂-C₂₂ alkylmethacrylatecopolymer, polyethylene, waxes,VP/dimethiconylacrylate/polycarbamylpolyglycol ester, butylated PVP,PVP/hexadecene copolymer, octadecene/MA copolymer, PVP/eicosenecopolymer, tricontanyl PVP, Brassica Campestris/Aleuritis fordi Oilcopolymer, decamethyl cyclopentasiloxane (and) trimethylsiloxysilicate,and mixtures thereof. In some cases, the film former isacrylates/C₁₂-C₂₂ alkylmethacrylate copolymer sold under the tradenameAllianz OPT® by ISP.

Many of the common film-forming polymers included in sunscreencompositions are not soluble in ethanol (such as PVP/Eicosenecopolymer). A common film-former employed in ethanol based sunscreenproducts is Dermacryl LT or Dermacryl 79 marketed by Akzo Nobel (INCIName: acrylates/octylacrylamide copolymner). Dermacryl LT (CAS Number:80570-62-3) is a hydrophobic, high molecular weight carboxylated acryliccopolymer. It functions as a film-former in a broad range of cosmeticformulations, imparting waterproofing, increased occlusivity anddecreased rub-off of actives.

The total amount of film-formers present in the compositions istypically in an amount of about 0.1, 0.5, 1.0, or 5 wt. % to about 5,10, 20, or 25 wt. %, based on the total weight of the composition.

Emulsifiers

The sunscreen compositions typically include at least one emulsifiersuch as an amphoteric, anionic, cationic or nonionic emulsifier, usedalone or as a mixture, and optionally a co-emulsifier. The emulsifiersare chosen in an appropriate manner according to the emulsion to beobtained (W/O or O/W). The emulsifier and the co-emulsifier aregenerally present in the composition in a proportion ranging from 0.3%to 30% by weight and preferably from 0.5% to 20% by weight relative tothe total weight of the composition.

For W/O emulsions, examples of emulsifiers that may be mentioned includedimethicone copolyols, such as the mixture of cyclomethicone anddimethicone copolyol sold under the trade name DC 5225 C by the companyDow Corning, and alkyl dimethicone copolyols such as the lauryldimethicone copolyol sold under the name Dow Corning 5200 FormulationAid by the company Dow Corning, and the cetyl dimethicone copolyol soldunder the name Abil EM 90™ by the company Goldschmidt. A crosslinkedelastomeric solid organopolysiloxane comprising at least one oxyalkylenegroup, such as the product sold under the reference KSG 21 by thecompany Shin-Etsu, may also be used as surfactants for W/O emulsions.

For O/W emulsions, examples of emulsifiers that may be mentioned includenonionic emulsifiers such as oxyalkylenated (more particularlypolyoxyethylenated) fatty acid esters of glycerol; oxyalkylenated fattyacid esters of sorbitan; oxyalkylenated (oxyethylenated and/oroxypropylenated) fatty acid esters; oxyalkylenated (oxyethylenatedand/or oxypropylenated) fatty alcohol ethers; sugar esters such assucrose stearate; and mixtures thereof.

The fatty acid esters of a sugar that can be used as nonionicamphiphilic lipids can be chosen in particular from the group comprisingesters or mixtures of esters of a C₈-C₂₂ fatty acid and of sucrose, ofmaltose, of glucose or of fructose, and esters or mixtures of esters ofa C₁₄-C₂₂ fatty acid and of methylglucose.

The C₈-C₂₂ or C₁₄-C₂₂ fatty acids forming the fatty unit of the estersthat can be used in the emulsion comprise a saturated or unsaturatedlinear alkyl chain having, respectively, from 8 to 22 or from 14 to 22carbon atoms. The fatty unit of the esters can be chosen in particularfrom stearates, behenates, arachidonates, palmitates, myristates,laurates, caprates and mixtures thereof.

By way of example of esters or of mixtures of esters of a fatty acid andof sucrose, of maltose, of glucose or of fructose, mention may be madeof sucrose monostearte, sucrose distearate, sucrose tristearate andmixtures thereof, such as the products sold by the company Croda underthe name Crodesta F50, F70, F110 and F160 having, respectively, an HLB(Hydrophilic Lipophilic Balance) of 5, 7, 11 and 16; and, by way ofexample of esters or of mixtures of esters of a fatty acid and ofmethylglucose, mention may be made of the disearate of methylglucose andof polyglycerol-3, sold by the company Goldschmidt under the nameTego-care 450. Mention may also be made of glucose monoesters or maltosemonoesters, such as methyl O-hexadecanoyl-6-D-glucoside andO-hexadecanoyl-6-D-maltoside.

The fatty alcohol ethers of a sugar that can be used as nonionicamphiphilic lipids can be chosen in particular form the group comprisingethers or mixtures of ethers of a C₈-C₂₂ fatty alcohol and of glucose,of maltose, of sucrose or of fructose, and ethers or mixtures of ethersof a C₁₄-C₂₂ fatty alcohol and of methylglucose. They are in particularalkylpolyglucosides.

The C₈-C₂₂ or C₁₄-C₂₂ fatty alcohols forming the fatty unit of theethers that can be used in the emulsion of the instant disclosurecomprise a saturated or unsaturated linear alkyl chain having,respectively, from 8 to 22 or from 14 to 22 carbon atoms. The fatty unitof the ethers can be chosen in particular from decyl, cetyl, behenyl,arachidyl, stearyl, palmityl, myristyl, lauryl, capryl and hexadecanoylunits, and mixtures thereof such as cetearyl.

By way of example of fatty alcohol ethers of a sugar, mention may bemade of alkylpolyglucosides, such as decylglucoside and laurylglucosidesold, for example, by the company Henkel under the respective namesPlantaren 2000 and Plantaren 1200, cetostearylglucoside, optionally as amixture with cetostearyl alcohol, sold, for example, under the nameMontanov 68 by the company Seppic, under the name Tego-care CG90 by thecompany Goldschmidt and under the name Emulgade KE3302 by the companyHenkel, and also arachidylglucoside, for example in the form of themixture of arachidyl and behenyl alcohols and of arachidylglucoside soldunder the name Montanov 202 by the company Seppic.

Use is more particularly made, as nonionic amphiphilic lipid of thistype, of sucrose monostearate, sucrose distearate, sucrose tristearateand mixtures thereof, the distearate of methylglucose and ofpolyglycerol-3, and alkylpolyglucosides.

The glycerol fatty esters that can be used as nonionic amphiphiliclipids can be chosen in particular from the group comprising the estersformed from at least one acid comprising a saturated linear alkyl chainhaving from 16 to 22 carbon atoms, and from 1 to 10 glycerol units. Usemay be made of one or more of these glycerol fatty esters in theemulsion of the instant disclosure. These esters may be chosen inparticular from stearates, behenates, arachidates, palmitates andmixtures thereof. Stearates and palmitates are preferably used.

By way of example of a surfactant that can be used in the emulsion ofthe instant disclosure, mention may be made of decaglycerolmonostearate, distearate, tristearate and pentastearate (10 glycerolunits) (CTFA names: polyglyceryl-10 stearate, polyglyceryl-10distearate, polyglyceryl-10 tristearate, polyglyceryl-10 pentastearate),such as the products sold under the respective names Nikkol Decaglyn1-S, 2-S, 3-S and 5-S by the company Nikko, and diglyceryl monostearate(CTFA name: polyglyceryl-2 stearate) such as the product sold by thecompany Nikko under the name Nikkol DGMS.

The sorbitan fatty esters that can be used as nonionic amphiphiliclipids chosen in particular from the group comprising esters of aC₁₆-C₂₂ fatty acid and of sorbitan and oxyethylenated esters of aC₁₆-C₂₂ fatty acid and of sorbitan. They are formed from at least onefatty acid comprising at least one saturated linear alkyl chain, having,respectively, from 16 to 22 carbon atoms, and from sorbitol or fromethoxylated sorbitol. The oxyethylenated esters generally comprise from1 to 100 ethylene oxide units, and preferably from 2 to 40 ethyleneoxide (EO) units. These esters can be chosen in particular fromstearates, behenates, arachidates, palmitates and mixtures thereof.Stearates and palmitates are preferably used.

By way of example of sorbitan fatty ester and of an oxyethylenatedsorbitan fatty ester, mention may be made of sorbitan monostearate (CTFAname: sorbitan stearate) sold by the company ICI under the name Span 60,sorbitan monopalmitate (CTFA name: sorbitan palmitate) sold by thecompany ICI under the name Span 40, or sorbitan 20 EO tristearate (CTFAname: polysorbate 65) sold by the company ICI under the name Tween 65.

The ethoxylated fatty ethers are typically ethers made up of 1 to 100ethylene oxide units and of at least one fatty alcohol chain having from16 to 22 carbon atoms. The fatty chain of the ethers can be chosen inparticular from behenyl, arachidyl, stearyl and cetyl units, andmixtures thereof, such as cetearyl. By way of example of ethoxylatedfatty ethers, mention may be made of ethers of behenyl alcoholcomprising 5, 10, 20 and 30 ethylene oxide units (CTFA names:beheneth-5, beheneth-10, beheneth-20 and beheneth-30), such as theproducts sold under the names Nikkol BB5, BB10, BB20 and BB30 by thecompany Nikko, and the ether of stearyl alcohol comprising 2 ethyleneoxide units (CTFA name: steareth-2), such as the product sold under thename Brij 72 by the company ICI.

The ethoxylated fatty esters that can be used as nonionic amphiphiliclipids are esters made up of 1 to 100 ethylene oxide units and of atleast one fatty acid chain comprising from 16 to 22 carbon atoms. Thefatty chain of the esters can be chosen in particular from stearate,behenate, arachidate and palmitate units, and mixtures thereof. By wayof example of ethoxylated fatty esters, mention may be made of the esterof stearic acid comprising 40 ethylene oxide units, such as the productsold under the name Myrj 52 (CTFA name: PEG-40 stearate) by the companyICI, and the ester of behenic acid comprising 8 ethylene oxide units(CTFA name: PEG-8 behenate), such as the product sold under the nameCompritol HD5 ATO by the company Gattefosse.

The block copolymers of ethylene oxide and of propylene oxide that canbe used as nonionic amphiphilic can be chosen in particular frompoloxamers and in particular from Poloxamer 231, such as the productsold by the company ICI under the name Pluronic L81 of formula (V) withx=z=6, y=39 (HLB 2); Poloxamer 282, such as the product sold by thecompany ICI under the name Pluronic L92 of formula (V) with x=z=10, y=47(HLB 6); and Poloxamer 124, such as the product sold by the company ICIunder the name Pluronic L44 of formula (V) with x=z=11, y=21 (HLB 16).Suitable hydrophobically-modified emulsifiers include, for example,inulin lauryl carbamate, commercially available from Beneo Orafti underthe tradename Inutec SP1.

The total amount of emulsifier present in the compositions is typicallyin an amount of about 0.1, 0.2, or 0.5 wt. % to about 4.0, 5.0, 6.0, or7.5 wt. %, based on the total weight of the composition.

Gelling Agent

Gelling agents may also be included in the sunscreen compositions.Examples of suitable hydrophilic gelling agents include beeswax,carboxyvinyl polymers such as the Carbopol products (carbomers) and thePemulen products (acrylate/C10-C30-alkylacrylate copolymer);polyacrylamides, for instance the crosslinked copolymers sold under thenames Sepigel 305 (CTFA name: polyacrylamide/C13-14 isoparaffin/Laureth7) or Simulgel 600 (CTFA name: acrylamide/sodium acryloyldimethyltauratecopolymer/isohexadecane/polysorbate 80) by the company SEPPIC;2-acrylamido-2-methylpropanesulfonic acid polymers and copolymers, whichare optionally crosslinked and/or neutralized, for instance thepoly(2-acrylamido-2-methylpropanesulfonic acid) (CTFA name: ammoniumpolyacryldimethyltauramide); cellulose-based derivatives such ashydroxyethyl-cellulose and hydroxypropyl methyl cellulose;polysaccharides and especially gums such as xanthan gum or Arabic gum;and mixtures thereof.

Lipophilic gelling agents (thickeners) that may be mentioned includemodified clays such as hectorite and its derivatives, for instance theproducts sold under the name bentone.

In some instances, the gelling agent is ammoniumacryloyldimethyltaurate/steareth-25 methacrylate crosspolymer,commercially available from Clariant under the tradename Aristoflex HMS.

The gelling agent is typically used in an amount of about 0.05 to about1.5% by weight, from about 0.08 to about 1.0% by weight, or about 0.1 toabout 0.5% by weight, based on the total weight of the composition.

Examples of dermatologically acceptable carriers for polyhydroxyfullerenes that have been specifically tested by the inventors include:Hydroxy propyl methyl cellulose (HPMC) (5%); Sodium stearate (0.5%);Glycerin (5-30%); Edible oils including coconut oil and olive oil;Water-in-oil emulsion; Polyethylene glycol (5-50%); Brij 99 (0.01-10%);Collagen; HPMC (1-5%)+Glycerin (1-25%); Beeswax (0-5%)+HPMC (0-10%)+Brij99 (0-5%)+Stearic acid (0-5%)+PHF (0.1-10%)+Cetyl alcohol (0-5%)+Stearylalcohol (0-5%)+Glycerin (0-10%)+Isopropyl palmitate (0-5%)+Brij 52(0-5%)+Glycerin trioctanoate (0-5%)+Deionized water (to total 100%); andXanthan gum (0-10%)+Stearic acid (0-25%)+K₂CO₃ (0-2%)+NaOH(0-2%)+Glycerin (0-30%)+PHF (0.1-10%)+Deionized water (to total 100%).

The present invention is illustrated by the following examples. It is tobe understood that the particular examples, materials, amounts, andprocedures are to be interpreted broadly in accordance with the scopeand spirit of the invention as set forth herein.

EXAMPLES Example 1: Comparison of PHF with Conventional SunscreenCompositions

The inventors discovered that PHF absorbs UV more effectively thancommercial sunscreens. For initial comparisons (FIG. 2), the UV-Visabsorption of PHF solution at 0.5 mg/mL (prepared in 25% glycerol) wascompared with Neutrogena SPF 60 (4.9% Titanium dioxide and 4.7% Zincoxide) sunscreen at 5 mg/mL (in de-ionized water). The totalconcentration of AI in the commercial sunscreen suspension was equal tothat of PHF (0.5 mg/mL) solution. PHF is a broad spectrum UV absorber,as its critical wavelength of 381 nm and UVA/UVB ratio of 1.6 exceedsthe FDA limit of 370 nm and 0.91, respectively. The absorbance of PHF is2.5-1.9 times higher in the UVB region (280-320 nm) and 1.9-1.5 timeshigher in the UVA region (320-400 nm) than SPF60 sunscreen. This high UVabsorptive ability of PHF (for preventing direct damage from UVB andUVA) becomes even more important when combined with other potentialadvantages of PHF (preventing indirect free radical mediated damage)over current sunscreen AIs, as summarized in Table 1 and FIG. 3.

TABLE 1 Advantages and limitations of actives used in sunscreenformulations and comparison with proposed polyhydroxy fullerene basedsunscreens. Items that include an asterix* indicate limitations.Inorganic UV Organic UV Polyhydroxy Properties absorbers absorbersFullerenes UVB absorption TiO₂, ZnO Octocrylene, PHF (280-320 nm)Octinoxate, Octisalate, Homosalate, etc. UVA absorption ZnO, TiO₂Avobenzone, PHF (320-400) Oxybenzone, etc. Stabilizers Not neededOctocrylene, Not needed Oxybenzone, Homosalate, etc. Antioxidants Can beHomosalate, Vitamin PHF degraded; C, Vitamin E, rarely used* EGCG, etc.Potential ROS TiO₂, ZnO* Octocrylene, None generation Oxybenzone, etc.*Photolabile No Avobenzone, No Octinoxate, Octisalate, etc.* ROS None*Yes* Catalytically susceptibility neutralizes ROS Phototoxicity Less*High, Not expected potential depending on the AI* Safety concerns Low*High* Not expected

Example 2: In Vivo Experiments

The inventors preliminary data show that PHF is not only effective inblocking UVB transmission in vitro (FIG. 2), but also in reducing damageto the skin in vivo (FIG. 4). In vivo experiments were carried out withhairless SKH-1 mice, a standard model for studying UV damage (Anand etal., J Invest Dermatol, 2005. 125(2): p. 323-33) and carcinogenesis (Kimet al., PLoS One, 2012. 7(6): p. e39691) in the skin. FIG. 4 shows datafrom initial experiments to examine PHF's effects upon UV-induciblebiomarkers in living mouse skin. PHF (obtained from MER Corp.) wasdissolved in water and applied on the right flank (2 cm×1 cm) of thedorsal region of hairless SKH-1 mice. The left flank (2 cm×1 cm) of thesame mouse was used as a control with topical application of deionizedwater. The topical applications were allowed to dry for 15 minutesfollowed by UV exposure (80 mJ/cm²; 90% UVB and 10% UVA). At 24 hoursafter UV exposure, the flanks of mice were observed for redness orerythema. PHF treated regions did not show any signs of erythema(sunburn), whereas control flanks were red indicating severe sunburn.Mice were euthanized 48 hours post-UV exposure, and the skin washarvested for histological analysis or immunofluorescent staining.Histological analysis of the skin showed (i) a marked reduction inepidermal cell death (dyskeratotic “sunburn cells”), compare FIGS. 4aand 4b ; (ii) faster recovery of proliferation (cell division occurring24-48 h after UVB), compare FIGS. 4c and 4d ; and (iii) fewer DNAphotoproducts (cyclopyrimidine dimers, CPD's) observed in skin treatedwith PHF, compare FIGS. 4e and 4 f.

Example 3: PHF Formulation

PHF is a single, multifunctional active that replaces multiple activesof current sunscreen formulations. A suitable vehicle for PHF wasdesigned that does not compromise the rheological properties requiredfor topical application of sunscreen. The concentration of PHF wasoptimized and the minimum concentration of PHF that prevents symptoms ofsunburn (erythema and edema) was determined. In a preclinical model,different skin sections were applied with PHF formulation, SPF60commercial sunscreen, vehicle (without PHF) samples and control (noapplication). All skin sections were exposed to UVB at 120 mJ/cm² dose.The skin sections were monitored for erythema (redness) and edema(swelling) at 24, 48 and 72 hours. Maximum erythema is usually observedat 48 hours. The photographs of skin sections at 48 hours were scored bya panel consisting of two dermatologists and two non-dermatologists. Thepanel was blinded to the identity of the samples. The scale used forscoring is shown in Table 2. The result of blinded scoring study isplotted in FIG. 5. PHF reduced erythema and edema significantly (α=0.01)compared to control and vehicle only formulations, and was on par withcommercial SPF60 sunscreen.

TABLE 2 Scale for scoring erythema and edema of skin SKIN REACTIONSSCORE Erythema and eschar formation None 0 Barely perceptible 1 Slighterythema (well-defined edges, pink throughout the 2 exposed area)Moderate erythema 3 Severe erythema (Beet red) with some ulceration 4Edema formation None 0 Barely perceptible 1 Slight edema (well-definededges, visible throughout the 2 exposed area) Moderate edema (raised ~1mm) 3 Severe edema (raised > 1 mm) 4

The complete disclosure of all patents, patent applications, andpublications, and electronically available material cited herein areincorporated by reference. The foregoing detailed description andexamples have been given for clarity of understanding only. Nounnecessary limitations are to be understood therefrom. The invention isnot limited to the exact details shown and described, for variationsobvious to one skilled in the art will be included within the inventiondefined by the claims.

What is claimed is:
 1. A sunscreen composition, comprising adermatologically acceptable carrier and a fullerene compound accordingto the formula C_(2n)(OH)_(t)(NH₂)_(v)(COOH)_(w)(COOM)_(x)O_(y)M_(z),wherein M is an alkali metal, alkaline earth metal, transition metal,post-transition metal, or lanthanide, n is a number ranging from 10 to270, t is number ranging from 1 to 60, v is a number ranging from 0 to60, w is a number ranging from 0 to 60, x is a numbering ranging from 0to 60, y is a number ranging from 1 to 30, and z is a number rangingfrom 1 to 10, and wherein (t+y) is greater than z.
 2. The sunscreencomposition of claim 1, wherein v, w, and x are
 0. 3. The sunscreencomposition of claim 1, wherein n is
 30. 4. The sunscreen composition ofclaim 1, wherein the sunscreen composition is essentially free ofnon-polyhydroxy fullerene sunscreen active agents.
 5. The sunscreencomposition of claim 1, wherein the sunscreen composition furthercomprises an antioxidant.
 6. The sunscreen composition of claim 1,wherein the sunscreen composition further comprises an active ingredientselected from the group consisting of para-aminobenzoic acid (PABA),octinoxate,3-(4″trimethylammonium)-benzyliden-bornan-2-on-methylsulfate,octocrylene, octylsalicylate, benzophenone-3, benzophenone-4,benzophenone-8, avobenzone, ecamsule, silatrizol, and homosalate.
 7. Thesunscreen composition of claim 1, wherein the fullerene compound isencapsulated.
 8. The sunscreen composition of claim 1, wherein thedermatologically acceptable carrier is a lotion, ointment, gel, spray,or cream.
 9. The sunscreen composition of claim 1, wherein the sunscreencomposition provides a sun protection factor (SPF) value of at least 10.10. The sunscreen composition of claim 1, wherein w and x are
 0. 11. Thesunscreen composition of claim 1, wherein w and x are 0, and y and z are1.